HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers

Shuling Ren, Daria A. Gaykalova, Theresa Guo, Alexander V. Favorov, Elana J. Fertig, Pablo Tamayo, Juan Luis Callejas-Valera, Mike Allevato, Mara Gilardi, Jessica Santos, Takahito Fukusumi, Akihiro Sakai, Mizuo Ando, Sayed Sadat, Chao Liu, Guorong Xu, Kathleen M. Fisch, Zhiyong Wang, Alfredo A. Molinolo, J. Silvio GutkindTrey Ideker, Wayne M. Koch, Joseph A. Califano

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy.

Original languageEnglish
Pages (from-to)6327-6339
Number of pages13
JournalOncogene
Volume39
Issue number40
DOIs
Publication statusPublished - Oct 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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